Magnetic targeting of smooth muscle cells in vitro using a magnetic bacterial cellulose to improve cell retention in tissue-engineering vascular grafts

Tissue-engineered vascular grafts (TEVG) use biologically-active cells with or without supporting scaffolds to achieve tissue remodeling and regrowth of injured blood vessels. However, this process may take several weeks because the high hemodynamic shear stress at the damaged site causes cellular denudation and impairs tissue regrowth. We hypothesize that a material with magnetic properties can provide the force required to speed up re-endothelization at the vascular defect by facilitating high cell density coverage, especially during the first 24 h after implantation. To test our hypothesis, we designed a magnetic bacterial cellulose (MBC) to locally target cells in vitro under a pulsatile fluid flow (0.514 dynes cm^-2). This strategy can potentially increase cell homing at TEVG, without the need of blood cessation. The MBC was synthesized by an in situ precipitation method of Fe³⁺ and Fe²⁺ iron salts into bacterial cellulose (BC) pellicles to form Fe₃O₄ nanoparticles along the BC's fibrils, followed by the application of dextran coating to protect the embedded nanoparticles from oxidation. The iron salt concentration used in the synthesis of the MBC was tuned to balance the magnetic properties and cytocompatibility of the magnetic hydrogel. Our results showed a satisfactory MBC magnetization of up to 10 emu/g, which is above the value considered relevant for tissue engineering applications (0.05 emu/g). The MBC captured magnetically-functionalized cells under dynamic flow conditions in vitro. MBC magnetic properties and cytocompatibility indicated a dependence on the initial iron oxide nanoparticle concentration.

Statement of significance: Magnetic hydrogels represent a new class of functional materials with great potential in TVEG because they offer a platform to (1) release drugs on demand, (2) speed up tissue regrowth, and (3) provide mechanical cues to cells by its deformability capabilities. Here, we showed that a magnetic hydrogel, the MBC, was able to capture and retain magnetically-functionalized smooth muscle cells under pulsatile flow conditions in vitro. A magnetic hydrogel with this feature can be used to obtain high-density cell coverage on sites that are aggressive for cell survival such as the luminal face of vascular grafts, whereas simultaneously can support the formation of a biologically-active cell layer that protects the material from restenosis and inflammation.